Objective: To study the relationship between human papilloma virus (HPV) infection and abnormal expression of p53 protein in oral squamous cell carcinoma (OSCC). Materials and Methods: A total of 50 biopsy specimens from patients with OSCC were studied. Molecular biological and immunohistochemical methods were used to detect HPV infection in OSCC and abnormal expression of p53 protein. Results: Of the 50 specimens, 14 showed HPV DNA. HPV type 16 was dominant, and one case was infected with HPV type 16 and 18. There were 9 cases of HPV infection in 24 samples with p53 overexpression, and 5 cases in 15 samples without p53 overexpression. Conclusions: HPV type 16 and 18 seem to be risk factors in oral carcinoma development. However, results are greatly varied, from 5% to 95%. The cause may be due to sensitivity of detection methods and the number of samples. Regarding p53 expression, the present study shows that the HPV infection and p53 expression in oral cancer are not closely related. Palabras clave: human papilloma virus (HPV), oral cancer, p53